Role of Everolimus in Highly Sensitized Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Role of Everolimus in Highly Sensitized Patients (NCT01911546), a na phase 2 study. The primary outcome is The Number of Polyoma BK Viremia Patients.

2. Clinical Question

3. Trial Design

This was a prospective, single-group phase 2 pilot trial titled “Role of Everolimus in Highly Sensitized Patients.” Its official title describes an evaluation of safety and tolerability of everolimus for prevention of BK and CMV viremia in HLA-sensitized kidney transplant recipients. The study is listed as completed, with enrollment of 20 participants. Its start is recorded as 2013-06 and its primary completion as 2016-01.

Participants were assigned to the listed regimen of everolimus with low-dose tacrolimus. The arm description says patients receiving everolimus would be on low-dose tacrolimus. The trial is not described as randomized, and masking is listed as none. With a single group and no comparator, the design can describe outcomes among participants receiving the regimen but cannot isolate a treatment effect by comparing outcomes with a concurrent control group.

The registry background explains the clinical motivation: highly sensitized recipients are at risk of BK virus and CMV infection after transplant, and the record also discusses concerns about rejection and difficulties associated with leukopenia and CMV prophylaxis. These statements describe the rationale in the registry; they are not trial findings.

The primary endpoint is the number of participants with Polyoma BK viremia over 12 months. Incidence of cell-mediated rejection is listed as a secondary outcome. The registry record does not report the endpoint results or the detailed analysis plan. In particular, it does not state how the study handled incomplete monitoring, defined evaluable participants, or analyzed the secondary outcome.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: A total of 20 patients were enrolled in this clinical trial.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Polyoma BK Viremia Patients, measured over 12 months.

The primary endpoint is the number of participants with Polyoma BK viremia during a 12-month timeframe. The registry describes regular monitoring for the development of Polyomavirus viremia. The endpoint is a participant count: it concerns how many people met the endpoint, rather than the number of viral measurements or the level of virus in each participant.

As a general statistical point, an endpoint based on whether participants experience an event can describe the occurrence of that event in the study group. It does not, by itself, show when the event began, how long it lasted, or how severe it was. Those questions would require separately defined measures and reported results. The registry record does not specify the precise diagnostic threshold for viremia, the schedule of monitoring, or how repeated positive measurements were counted.

Monitoring for BK viremia is relevant to the study’s stated focus on viral infection after kidney transplantation. The primary endpoint can therefore describe an aspect of the trial’s stated safety and prevention question. However, the endpoint result is not reported in the registry record. No event count, estimate of frequency, or uncertainty interval can be interpreted from the posted endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the endpoint represents. The primary outcome is a count of participants with Polyoma BK viremia over 12 months. As a general statistical explanation, a participant-level event endpoint classifies each person according to whether the defined event occurred during the specified observation period. To interpret such an endpoint fully, readers need a clear event definition, a clear observation period, and a description of how incomplete observations are handled. The registry says participants would be monitored at regular intervals, but the detailed schedule and diagnostic threshold are not reported in the registry record.

For a single-group study, an event count can be described relative to the number of participants assessed. General methods for binary outcomes often estimate the event probability and quantify uncertainty around it. The registry record does not provide the primary event count, an estimate, or an uncertainty interval, so none of those quantities can be interpreted for this trial. No new estimate can be recovered from the enrollment figure alone: enrollment does not establish how many participants had complete endpoint monitoring.

What a comparison would require. In general, a comparative treatment analysis needs outcomes for groups that can be meaningfully contrasted, along with a method addressing how participants entered those groups. This study is listed as single group, allocation is not applicable, and no comparator is described. The data structure therefore supports no randomized contrast. Any simple comparison with an external population would require information and assumptions not reported in the registry record, and would not be equivalent to a randomized trial comparison.

Uncertainty and confidence intervals. In general, a confidence interval expresses the uncertainty of an estimate under a specified statistical procedure and its assumptions. A narrow interval indicates greater precision than a wide interval, but interval width does not determine whether a result is clinically important. No confidence interval for the primary endpoint is reported in the registry record. Without the outcome count and an analysis method, the precision of the endpoint cannot be assessed.

Analysis plan and sample-size illustrations. The analysis information lists no analyses. The statistical analysis plan, including any model for the primary endpoint, is not reported in the registry record. The record also gives planning-illustration assumptions: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are described as an illustration computed from the observed effect, not as the trial’s own design. They should not be read as the trial’s prespecified sample-size justification or as observed power. The trial itself is a single-group study, so the equal-allocation, two-arm assumption belongs to the planning illustration rather than the listed trial design.

As a general principle, power is a design-stage probability tied to specified assumptions about an effect, variability, sample size, and analysis. It is not a measure of how likely a reported finding is to be true. A retrospective power calculation based on an observed estimate adds little information beyond that estimate and its uncertainty. The registry record does not report the trial’s sample-size justification, target effect, or a prespecified power calculation.

Multiplicity and secondary outcomes. The registry lists four outcome measures and identifies incidence of cell-mediated rejection as a secondary outcome. When a study evaluates multiple outcomes or multiple analyses, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches include prespecifying a primary outcome, adjusting for multiple testing, or treating secondary results as exploratory. The registry record does not report a multiplicity strategy or the results of the secondary outcome. The other outcome details are not reported in the registry record.

Counts are not the whole clinical picture. A participant count does not convey event timing, duration, severity, or repeated episodes unless those features are separately defined and reported. General count-based summaries can also obscure differences in observation time when participants are followed for unequal periods. The listed primary timeframe is 12 months, but the record does not say how individual follow-up duration or missed monitoring was handled. No time-to-event analysis is reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Everolimus + Low-dose Tacrolimus")
n      <- c(20)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Everolimus + Low-dose Tacrolimus  20  5  25.0  8.7  49.1  11.2  46.9  11.3  47.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary BK viremia endpoint and incidence of cell-mediated rejection as a secondary outcome. The details for the other outcome measures are not reported in the registry record. No multiplicity procedure is described. As a general statistical issue, examining multiple outcomes can increase the chance of a seemingly notable result arising by chance; prespecifying a primary outcome helps clarify which question is central, but does not itself explain how secondary results were handled.

The analysis information lists no analyses, and the statistical analysis plan is not reported in the registry record. There is no reported description of an intention-to-treat population, a per-protocol population, or another analysis population. The record does not explain whether all enrolled participants were included in each outcome analysis or how participants were classified if outcome information was unavailable.

Missing endpoint data can affect both the estimated event frequency and its uncertainty. In general, methods may depend on why measurements are missing and how much information is absent; assumptions about missingness should be stated rather than silently treated as fact. The registry says participants would be monitored at regular intervals, but it does not report monitoring completion, losses to follow-up, missing observations, or imputation methods. Enrollment of 20 does not establish that endpoint data were available for all 20.

Because the primary result and its analysis details are absent, readers cannot assess the effect of missing data, the handling of multiple outcomes, or the population on which any estimate was based.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urine leak (10.0%), edema (5.0%), antibody mediated rejection and thrombotic microangiopathy (5.0%), antibody mediated rejection / fsgs /small bowel obstruction/dehydration (5.0%), inguinal hernia (5.0%).

The serious adverse-event summary lists 20 participants at risk, with 9 affected, and 0 deaths. The other adverse-event summary lists 20 participants at risk, with 20 affected. These are descriptive counts from the registry record and do not establish whether an event was caused by the regimen.

The listed serious-event terms and percentages are: Urine Leak, 10.0%; Edema, 5.0%; Antibody Mediated Rejection and Thrombotic Microangiopathy, 5.0%; Antibody Mediated Rejection / FSGS /Small Bowel Obstruction/Dehydration, 5.0%; Inguinal Hernia, 5.0%; and Shortness of Breath and Atrial Fibrillation, 5.0%. The record does not explain the event-counting rules, whether participants could appear under more than one term, or whether the grouped terms represent individual events or combined reporting categories. The terms should therefore be read as registry-listed categories, not assumed to be mutually exclusive.

As a general point, adverse-event summaries describe events observed during a study; without a comparison group, they cannot show whether the regimen changes event risk relative to another condition. The record does not provide a comparative safety analysis or causal attribution for these events.

13. What the Result Does, and Does Not, Mean

The registry record establishes that a completed, single-group phase 2 pilot enrolled 20 highly sensitized kidney transplant recipients and studied everolimus with low-dose tacrolimus. It identifies monitoring for Polyoma BK viremia over 12 months as the primary endpoint and lists cell-mediated rejection as a secondary outcome. It also reports descriptive adverse-event counts and terms.

It does not report the primary BK viremia result. As a result, the posted information cannot show the number of participants who experienced that endpoint, estimate its frequency, or describe the precision of an estimate. The absence of a reported result should not be interpreted as no events, nor as evidence that the endpoint was or was not met.

The study’s single-group design means that even a reported outcome count would describe what occurred in the enrolled group rather than provide a randomized treatment comparison. Without a comparator, the record cannot separate outcomes associated with the study regimen from outcomes that might have occurred for other reasons. This is particularly important when interpreting the registry background: statements about infection risk, rejection, and the rationale for studying everolimus explain why the question was considered, but they are not trial results.

The adverse-event figures describe events recorded in the study group, including serious events and other events. They do not establish causation or relative safety. The registry does not report an analysis linking adverse events to treatment exposure or a comparison with another group.

In short, the record is informative about the trial’s stated clinical question, design, regimen, enrollment, and some safety summaries. It is not sufficient to determine the observed primary endpoint or to support a comparative conclusion about treatment effects. Those limits reflect what is reported in the registry record, rather than a conclusion about what happened to participants beyond the posted information.

14. Why This Trial Matters Statistically

This trial addresses a focused statistical question: how many highly sensitized kidney transplant recipients receiving everolimus with low-dose tacrolimus experienced Polyoma BK viremia during the 12-month monitoring period? Clearly defining the outcome and its observation window matters because they determine what the resulting count describes. The registry record identifies that question and labels the study as a prospective pilot.

The design is also essential to interpretation. A single-group study can provide descriptive information about outcomes among enrolled participants. It does not, by itself, estimate how outcomes would differ under another treatment. Readers need to distinguish a treatment’s rationale from a treatment effect, and an observed event count from a comparative estimate. Here, the registry does not report the primary event count, so even the descriptive answer to the stated endpoint is unavailable.

The record illustrates why enrollment, analysis populations, follow-up completeness, and endpoint results should not be treated as interchangeable. Enrollment was 20, but the record does not report the number with complete endpoint monitoring or the primary result. Without those details, neither the endpoint frequency nor its precision can be assessed.

Finally, safety summaries have their own interpretation limits. Counts and listed event categories can document what was recorded, but they do not establish causation, relative risk, or a treatment difference without an appropriate comparison and analysis. The registry’s serious-event information is therefore useful as a description of reported events, while remaining insufficient for comparative conclusions.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting efficacy-related outcomes is that the primary endpoint result is not reported in the registry record. The record gives the endpoint definition in broad terms and a 12-month timeframe, but not the observed number of participants with BK viremia, an estimate, or an uncertainty interval. The precise diagnostic threshold and monitoring schedule are also not reported.

The trial is listed as single group, with no comparator and no random allocation. Consequently, the design does not provide a randomized contrast for assessing differences in outcomes between treatment conditions. The absence of a comparison is especially relevant when considering the registry background, which describes infection and rejection concerns but does not constitute evidence of treatment effects.

The enrolled group was 20 participants, and no further detail about participant characteristics is reported in the registry record used for this analysis. The record does not describe endpoint completeness, losses to follow-up, missing-data handling, or which analysis population was used. Enrollment alone cannot establish how many participants contributed data to a particular endpoint.

The registry identifies a secondary outcome and reports four outcome measures overall, but the full analysis plan, multiplicity handling, and results for the secondary outcome are not reported. The adverse-event summary includes serious and other events, but the record does not explain event adjudication, attribution, overlap among listed terms, or comparative analyses. These limitations restrict both the assessment of outcome precision and the scope of conclusions that can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Role of Everolimus in Highly Sensitized Patients — NCT01911546.
• Registry record last updated 2017-12-07; status last verified 2017-11.
• Results first posted 2017-12-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01911546 is a completed phase 2 prospective pilot trial titled “Role of Everolimus in Highly Sensitized Patients.” It enrolled 20 participants and studied everolimus with low-dose tacrolimus in a single group, without masking or a comparator. The primary endpoint was the number of participants with Polyoma BK viremia over 12 months; the registry describes regular monitoring. Incidence of cell-mediated rejection is listed as a secondary outcome.

The registry record does not report the primary endpoint result, a statistical analysis plan, or details of missing-data handling and analysis populations. It lists 9 participants affected by serious adverse events, 20 affected by other adverse events, and 0 deaths. These safety figures are descriptive and do not establish causation or comparative risk. The record therefore outlines the trial question and design, but does not provide the result needed to assess the primary BK viremia endpoint.